Sulfuric Acid → 4-Nitro-3-phenyl-L-alanine

HRID 1271224Notes

Reaction equation

HRID 1271224 reaction equation
C([NH:11][C@H:12]([C:23]([OH:25])=[O:24])[CH2:13][C:14]1[CH:19]=[CH:18][C:17]([N+:20]([O-:22])=[O:21])=[CH:16][CH:15]=1)(OCC1C=CC=CC=1)=O.CC(=C)C.S(=O)(=O)(O)O.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.C(=O)=O.C(OCC)(=O)C>[N+:20]([C:17]1[CH:16]=[CH:15][C:14]([CH2:13][C@@H:12]([C:23]([OH:25])=[O:24])[NH2:11])=[CH:19][CH:18]=1)([O-:22])=[O:21]

Participants

8

Reactant 4

HCID 1118Sulfuric AcidHCID 8255IsobutyleneHCID 10340Sodium CarbonateHCID 12086111Cbz-4-nitrophenylalanine

Product 1

HCID 137064-Nitro-3-phenyl-L-alanine

Reagents, catalysts & solvents 3

HCID 280Carbon DioxideSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

The Cbz-4-nitrophenylalanine, 19D, (75 g, 0.22 mol) was dissolved in dioxane (300 mL). The resulted stirred solution was cooled in dry ice bath to −20° C. (internal). The liquefied isobutylene (approx. 290 mL) was added followed by conc. sulfuric acid (35 mL) added in three equal portions, 30 min apart. The addition of acid is a very exothermic process, accompanied by substantial degree of polymerization. Efficient mechanical stirring is essential at this stage. Resulted mixture was stirred for 20 hr, allowing to warm up to ambient temperature then was cautiously poured into sat. aq. sodium carbonate solution (2 L) and diluted with ethyl acetate (600 mL). Organic layer was separated and aqueous layer was extracted with ethyl acetate (2×200 mL). Combined extracts were washed with water and dried with sodium sulfate. Obtained solution was filtered and evaporated to dryness. Residue was taken up in ethyl acetate/hexane mixture (500 mL; 1:1) and filtered through plug of silica gel (ca. 2×2 inches). Silica was rinsed with additional amount of the same solvent (2 L total) and filtrates were evaporated to give fully protected 4-nitrophenylalanine as a viscous oil, 73 g (83% after two steps) 19E. 1H-NMR, CDCl3, (δ): 8.12 (d, 2H, J=8.4 Hz), 7.36 (m, 7H), 5.35 (m, 1H), 5.10 (m, 2H), 4.57 (m, 1H), 3.31 (m, 2H), 1.43 (s, 9H). 13C-NMR, CDCl3, (δ): 169.7, 155.3, 146.9, 143.9, 136.0, 130.2, 128.4, 128.2, 128.0, 123.3, 82.9, 66.9, 54.7, 38.2, 31.4, 27.8, 13.9.

Workup

  1. additionadded in three equal portions, 30 min apart
  2. additionThe addition of acid
  3. customaccompanied by substantial degree of polymerization
  4. stirringEfficient mechanical stirring
  5. customResulted mixture
  6. stirringwas stirred for 20 hr
  7. customOrganic layer was separated
  8. extractionaqueous layer was extracted with ethyl acetate (2×200 mL)
  9. washCombined extracts were washed with water
  10. dry with materialdried with sodium sulfate
  11. filtrationObtained solution was filtered
  12. customevaporated to dryness
  13. filtrationfiltered through plug of silica gel (ca. 2×2 inches)
  14. washSilica was rinsed with additional amount of the same solvent (2 L total) and filtrates
  15. customwere evaporated

Sources & evidence

ORD record
ord-327eb349e4ff403ea6796a40ba3a70a5
Source dataset
uspto-grants-2007_04
Patent number
US07205310B2

Reaction notes

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